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Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is an autosomal recessive blistering disease including lethal and non-lethal variants due to mutations in ITGB4 and ITGA6. It is unclear whether PA is caused directly by the mutations in these genes or by other factors. Skin biopsies from patients with JEB were processed for immunofluorescence mapping. When staining for integrin β4 or α6 was absent or reduced, ITGB4 was screened for mutations. A review of known mutations of ITGB4 and the phenotypes of patients with JEB-PA was undertaken. Three novel ITGB4 mutations were identified in 3 families with JEB-PA: 2 splice-site and one insertion mutation. Two families with lethal phenotypes (EB-050 and EB-049) were due to combinations of premature termination codons and missense mutations (658delCIR252C and 3903dupC/G273D, respectively). The third family EB-013 has 2 JEB affected siblings; a brother with PA and a sister without PA. Both were homozygous for ITGB4 264G>A/3111-1G>A. Two cases had no gastrointestinal symptoms or signs of PA. PA is an inconstant feature of the subtype of epidermolysis bullosa known as JEB-PA. It is most likely that multiple factors influence the development of PA and its presence is not predictive of a poor outcome. It is possible that institutions that do not routinely screen immunofluorescence mapping for integrin α6β4 staining in the absence of PA are missing this form of epidermolysis bullosa. [ABSTRACT FROM AUTHOR]